SAXS for Pharmaceuticals
Traditional pharmaceutical therapies are typically synthesized by chemical reaction and are undergoing a steady change to address more diverse disease pathways and hit more challenging targets. The result generates beyond the rule of five molecules, such as PROTACS, peptides and oligonucleotides, that present poor solubility or stability. These drug substances often require precise control of the material properties and complex formulation in order to deliver the dose reproducibly. Meanwhile, generics manufacturers face greater complexity when deformulating these products to produce lower cost alternatives.
Challenges
Solubility problems cut two ways.
Novel molecules either lock into strong crystal lattices as “brick dust” or turn highly lipophilic as “grease balls.” Each profile demands a different formulation strategy and nanoscale structure.
Amorphous stability comes at a cost.
Amorphous systems solve solubility, but only with a high polymer fraction and limited long-term stability. Controlling the amorphous phase at optimal drug loading remains a major challenge.
Oligos don't stay put.
Folding, cross-linking and aggregation form larger secondary structures, cutting biological function and manufacturing yield — and these behaviors can shift unpredictably during scale-up.
Complexity hides at the nanoscale.
Modern innovator products can’t be reduced to their components or formulation type. Real performance lives in amorphous domains, lamellar spacing and lipid structures.
Solution
Small-Angle and Wide-Angle X-ray Scattering (SAXS/WAXS) provide direct, non-destructive insight into the phases and stability of amorphous solid dispersions, the structures of lipid-based drug delivery systems and oligomeric states under processing conditions to develop manufacturing design spaces. Using this information scientists can accelerate formulation and drug development programs or indeed the development of generics and biosimilars.
Information obtained
Particle Size & Distribution
Quantify particle size distributions and monitor aggregation in pharmaceutical formulations.
Internal Structure & Layering
Characterize internal architecture, layering, and nanostructure in drug carriers and formulations.
Crystallinity & Amorphous Structure
Measure crystallinity, polymorphism, and amorphous ordering to understand stability and performance.
Self-Assembly & Formulation Structure
Characterize lipid nanoparticles, nanoemulsions, polymer-based delivery systems, and solid dispersions.
Structural Stability & Transformation
Track structural changes during mixing, heating, freeze–thaw cycles, dissolution, and storage using in situ and time-resolved measurements.
Development & Quality Control
Apply non-destructive structural characterization across solid, semi-solid, and solution states from early formulation development through manufacturing and QC.
Data example
In this example, an oligomeric state of a protein is shown to form from the monomer and then convert to a fibril. Sometimes oligomers are the desired product, other times they can reduce yield in manufacturing or be precursor states to aggregation. In this case, the protein is α-synuclein and fibrillation is a known pathway for neurodegeneration in Parkinson’s disease. The SAXS data illustrated the transient nature of this intermediate step under biorelevant conditions giving insight to the mechanism of formation.
Figure 1. SAXS curves of fibrillating aSN followed over time (from blue to red).
Typical Product Configurations
Nano-inXider
Low budget
Xeuss Pro
Mid budget
Xeuss Pro
High budget
Latest articles
